FDA Approves Alimta/Cisplatin for Malignant Mesothelioma

FDA Approves Alimta/Cisplatin for Malignant Mesothelioma

ROCKVILLE, MarylandThe Food and Drug Administration (FDA)
has approved Eli Lilly’s Alimta (peme-trexed disodium for injection) in
combination with cisplatin (Platinol) for the treatment of malignant pleural
mesotheli-oma in patients who are not candidates for curative surgery. Alimta,
an orphan drug, received priority review and is the first agent approved for
the treatment of the asbestos-related disease. The FDA’s action follows more
than 3 decades of efforts to develop an effective chemotherapy for malignant
pleural mesothelioma.

Physicians worldwide diagnose between 10,000 and 15,000 new
cases of the cancer annually, about 2,000 of them in the United States. The
incidence rate for the cancer, which develops in the inner lining of the chest
cavity, has been in-creasing. At diagnosis, most people who develop the disease
have progressed to an advanced stage where neither surgery nor radiation offers
a treatment option.

"For the first time ever, we have proof that a
chemotherapeutic regimen helps patients with malignant pleural mesothelioma
live longer," said Claude Denham, MD, a study coinvestigator for U.S. Oncology
and a medical oncologist with Texas Oncology in Dallas.

The FDA granted marketing approval to Alimta on the basis of
a multicenter, randomized, single-blind study in 448 patients with malignant
pleural mesothelioma from 19 countries who had not been treated previously with
chemotherapy. Patients’ ages ranged from 19 to 85; 81.5% were male, and 46% had
stage IV disease.

Study participants received either Alimta plus cisplatin
(226) or cisplatin alone (222). Alimta was given intrave-nously for 10 minutes
at a dose of 500 mg/m2. This treatment was followed about 30 minutes
later by a 2-hour infusion of cisplatin at 75 mg/m2. Both doses are
listed in the Alimta labeling.

After treating 112 patients, the researchers changed the
study protocol to require that all participants receive supplemental folic acid
and vitamin B12, to reduce hematologic and gastrointestinal (GI)
side effects.

Among the 448 patients in the study, median overall survival
was 12.1 months for the Alimta-treated patients vs 9.3 months for the cisplatin-only
arm, a 30% increase with Alimta. At 1 year, 50.3% of Alimta-treated patients
were alive, compared with 38% treated with cisplatin alone. In addition, there
was an improvement in lung function (forced vital capacity) on the Alimta/cisplatin
arm, compared with the cisplatin-only arm.

Among the 331 patients who received the full folic acid and
B12 supplementation, the median overall survival was 13.3 months in
the Alimta group vs 10.0 months in the cisplatin-only arm.

Among the fully supplemented patients, the Alimta-treated
arm received a median of six cycles of treatment vs four cycles for cisplatin
only. Patients who received no supplementation completed a median of two cycles
in each arm.

Adverse Events

Adverse events among the fully supplemented participants
consistently occurred more often in the Alimta-group than in the cisplatin-only
patients. For example, the rates for all stages of hematologic problems were
significantly higher for the treatment group vs the control groupneutropenia,
58% vs 16%; leukopenia, 55% vs 20%; anemia, 33% vs 14%; and thrombocytopenia,
27% vs 10%. "Complete blood cell counts, including platelet counts, should be
performed on patients receiving Alimta," the labeling cautions.

The drug’s labeling warns that physicians treating patients
with Alimta must instruct them "to take folic acid and vita-min B12
as a prophylactic measure to reduce treatment-related hematologic and GI
toxicity." It also states that patients should receive the drug only under the
supervision of a physician experienced in the use of antineoplastic agents.
Patients with kidney impairment should not receive Alimta therapy. Patients
should inform their doctors if they are taking nonsteroidal anti-inflammatory
drugs (NSAIDs).

In a press release, Eli Lilly said that it has submitted a
New Drug Application to the FDA for the use of single-agent Alimta in the
second-line treatment of non-small-cell lung cancer (NSCLC). The agent is also
being evaluated as first-line treatment of NSCLC, and in cancers of the
pancreas, colon, and breast.

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